Amiloride

Evidence Level: L5

Predicted Indications: 5

Amiloride

Pharmacist Assessment Report

Amiloride: potassium-sparing diuretic (ENaC blocker) → malignant hypertensive renal disease

One-Sentence Summary

Amiloride is a potassium-sparing diuretic that blocks the epithelial sodium channel (ENaC) and is marketed in Australia as a fixed-dose tablet with hydrochlorothiazide. The TxGNN model predicts it may be relevant to malignant hypertensive renal disease, with a score of 0.9982. No clinical trials and no publications were found for this disease, so the prediction rests on the model alone.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	malignant hypertensive renal disease
TxGNN Prediction Score	0.9982
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data are not available in the data compiled for this report. From what is generally known, amiloride blocks ENaC in the distal nephron. This reduces sodium reabsorption and potassium loss, giving a mild diuretic and blood-pressure-lowering effect. That offers a plausible link to hypertension-related kidney disease through volume and blood pressure control.

The caveats are substantial. Malignant hypertension is an acute, organ-threatening emergency. It is not managed with a slow-acting diuretic alone. Amiloride also carries risks of hyperkalaemia and of accumulation in renal impairment, which is a particular concern in kidney disease. The high score is a computational prediction, probably driven by closeness to hypertension-related diseases, and is not independent clinical evidence.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 13410T	Moduretic	Tablet containing hydrochlorothiazide 50 mg with amiloride hydrochloride 5 mg	Not recorded in the local data

Safety Considerations

Product Information warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI).

Drug Interactions: 136 interactions are recorded. Examples listed:

Moderate: hydrocortisone, betamethasone, budesonide, dexamethasone, metformin, bupropion, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, exenatide, bisacodyl, castor oil, glycerin, lactitol, lactulose, dronabinol
Minor: doxycycline, amoxicillin, cimetidine

Conditions flagged for caution in the compiled data: kidney disease, anuria, diabetic nephropathy, diabetes mellitus, diabetic ketoacidosis, liver disease, hepatic encephalopathy, gout, potassium deficiency disease, acidosis, pancreatitis, systemic lupus erythematosus and hyperparathyroidism. These come from relationship data, not from label text, and should be checked against the PI. Several are directly relevant to a patient with hypertensive kidney disease.

Conclusion and Next Steps

Decision: Hold

Rationale: No trials or publications address malignant hypertensive renal disease, so the evidence level is L5. The prediction is computational only. The clinical setting is an acute emergency in which amiloride is unlikely to be suitable, and there is a real risk of hyperkalaemia in impaired renal function.

To proceed, the following is needed:

Mechanism of action data and the PI warnings and contraindications
Any clinical or observational evidence in malignant hypertension or hypertensive nephropathy
A clear clinical role for amiloride relative to current standard care, with a renal and potassium safety assessment
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.